Biportal Endoscopic Spinal Cord Stimulation Paddle Lead Implantation: Technical Note and Preliminary Clinical Results.

OBJECTIVE: This study aims to elucidate a novel, minimally invasive surgical technique using a biportal endoscope for the implantation of spinal cord stimulation (SCS) paddle leads and to report the preliminary results of its clinical application. MATERIALS AND METHODS: The perioperative data of patients who underwent the biportal endoscopic SCS paddle lead implantation in our department were collected; the surgical procedure was delineated, and the clinical outcomes were assessed. RESULTS: From February 2022 to December 2023, six patients underwent biportal endoscopic SCS paddle lead implantation. The median follow-up time was nine months (range one to three months). The median intraoperative blood loss was 30 mL (range 25-50 mL), and the median operative time was 87.5 minutes (range 75-110 minutes). One patient experienced severe neck pain during the operation, whereas the other five patients experienced no surgical complications. One patient was found to have a slight lead migration three months after surgery, which did not affect the therapeutic effect. The median visual analogue scale (VAS) of the surgical area was 0.5 (range 0-2), 2.5 (range 1-4), and 0.5 (range 0-1) during the operation and one day and one week after the operation, respectively. The median VAS of the six patients' primary disease was 8 (range 7-9) before surgery and 2.5 (range 1-4) at the last postoperative follow-up (pain reduction ≥50%). CONCLUSION: Paddle lead systems for SCS can be implanted successfully using a biportal endoscopic technique.

Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma.

Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p < 0.001), Bacteroides (p = 0.018), and Ruminococcus (p = 0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances of Akkermansia and Bacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.

Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic-Device Using Prefilled Syringes and Autoinjectors.

Pharmacokinetic (PK) comparisons between therapeutic biologics have largely been based on the total area under the concentration-time curve (AUC) and the maximum concentration (Cmax ). For biologics with a long half-life, a PK comparability study may be long in duration and costly to conduct. The goal of this study was to evaluate whether a truncated AUC (tAUC) can be used to assess PK comparability when bridging prefilled syringe (PFS) and autoinjector (AI) treatment options for biologics with a long half-life. Fifteen biologics license applications (BLAs) were included to determine the concordance and geometric percent coefficient of variation (%CV) between tAUCs evaluated on days 7, 14, 21, and 28 and AUC evaluated to infinity (AUC0-inf ). Concordance is established if the tAUCs are comparable with AUC0-inf . Trial simulation was performed to examine the effect of the absorption rate constant (ka ) and sample size on the concordance of tAUCs. The tAUCs evaluated on day 14, 21, and 28 had 100% concordance with AUC0-inf for all 15 BLAs. The concordance of tAUC evaluated at day 7 was 87.5%. Based on the trial simulation, tAUC evaluated to day 28 post-dose can achieve high concordance (≥85%) for biologics exhibiting linear or nonlinear elimination with a ka of ≥0.1/day and with a sample size of 70 subjects per arm. tAUC appears to be a promising alternative PK measure, relative to AUC0-inf , for PK comparability assessments.

Population pharmacokinetics, pharmacodynamics and pharmacogenetics modelling of oxypurinol in Hmong adults with gout and/or hyperuricemia.

AIMS: The aim of this study was to quantify identifiable sources of variability, including key pharmacogenetic variants in oxypurinol pharmacokinetics and their pharmacodynamic effect on serum urate (SU). METHODS: Hmong participants (n = 34) received 100 mg allopurinol twice daily for 7 days followed by 150 mg allopurinol twice daily for 7 days. A sequential population pharmacokinetic pharmacodynamics (PKPD) analysis with non-linear mixed effects modelling was performed. Allopurinol maintenance dose to achieve target SU was simulated based on the final PKPD model. RESULTS: A one-compartment model with first-order absorption and elimination best described the oxypurinol concentration-time data. Inhibition of SU by oxypurinol was described with a direct inhibitory Emax model using steady-state oxypurinol concentrations. Fat-free body mass, estimated creatinine clearance and SLC22A12 rs505802 genotype (0.32 per T allele, 95% CI 0.13, 0.55) were found to predict differences in oxypurinol clearance. Oxypurinol concentration required to inhibit 50% of xanthine dehydrogenase activity was affected by PDZK1 rs12129861 genotype (-0.27 per A allele, 95% CI -0.38, -0.13). Most individuals with both PDZK1 rs12129861 AA and SLC22A12 rs505802 CC genotypes achieve target SU (with at least 75% success rate) with allopurinol below the maximum dose, regardless of renal function and body mass. In contrast, individuals with both PDZK1 rs12129861 GG and SLC22A12 rs505802 TT genotypes would require more than the maximum dose, thus requiring selection of alternative medications. CONCLUSIONS: The proposed allopurinol dosing guide uses individuals' fat-free mass, renal function and SLC22A12 rs505802 and PDZK1 rs12129861 genotypes to achieve target SU.

Hmong microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C): A phase II clinical study protocol.

BACKGROUND: Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C's effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual's multiomic signature may identify predictive markers of treatment success. OBJECTIVES: The primary objective of the Hmong Microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C) study was to assess the effectiveness of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The secondary objectives were to assess if 1) vitamin C impacts the taxonomic and functional patterns of microbiota; 2) taxonomic and functional patterns of microbiota impact vitamin C's urate-lowering effects; 3) genetic variations impact vitamin C's urate-lowering effects; 4) differential microbial biomarkers exist for patients with or without gout; and 5) there is an association between obesity, gut microbiota and gout/hyperuricemia. METHODS: This prospective open-labelled clinical trial was guided by community-based participatory research principles and conducted under research safety restrictions for SARS-CoV-2. We aimed to enroll a convenient sample of 180 Hmong adults (120 with gout/hyperuricemia and 60 without gout/hyperuricemia) who provided medical, demographic, dietary and anthropometric information. Participants took vitamin C 500mg twice daily for 8 weeks and provided pre-and post- samples of blood and urine for urate measurements as well as stool samples for gut microbiome. Salivary DNA was also collected for genetic markers relevant to uric acid disposition. EXPECTED RESULTS: We expected to quantify the impact of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The outcome will enhance our understanding of how gut microbiome and genomic variants impact the urate-lowering of vitamin C and associations between obesity, gut microbiota and gout/hyperuricemia. Ultimately, findings may improve our understanding of the causes and potential interventions that could be used to address health disparities in the prevalence and management of gout in this underserved population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04938024 (first posted: 06/24/2021).

Comparison of the Warfarin Dosing and Outcomes in Hmong Versus East Asians Patients: Real-World Data From an Integrated Healthcare System.

Background Previous research predicted that Hmong, an understudied East Asian subpopulation, might require significantly lower warfarin doses than East Asian patients partially due to their unique genetic and clinical factors. However, such findings have not been corroborated using real-world data. Methods This was a retrospective cohort study of Hmong and East Asian patients receiving warfarin. Warfarin stable doses (WSD) and time to the composite outcome, including international normalized ratio (INR) greater than four incidences or major bleeding within six months of warfarin initiation, were compared. Results This cohort study included 55 Hmong and 100 East Asian patients. Compared to East Asian patients, Hmong had a lower mean WSD (14.5 vs. 20.4 mg/week, p<0.05). In addition, Hmong had a 3.1-fold (95% CI: 1.1-9.3, p<0.05) higher hazard of the composite outcome. Conclusion Using real-world data, significant differences in warfarin dosing and hazard for the composite outcome of INR>4 and major bleeding were observed between Hmong and East Asian patients. These observations further underscore the importance of recognizing subpopulation-based differences in warfarin dosing and outcomes.

Knowledge and attitudes of incoming pharmacy students toward pharmacogenomics and survey reliability.

Aims: To assess knowledge and attitudes toward pharmacogenomics (PGx) of incoming doctoral pharmacy students, to evaluate the internal structure and reliability of the PGx survey and to identify variables associated with the different responses. Methods: A PGx survey based on the core pharmacist competencies in PGx was created. Results: Of 83.2% analyzable responses, 91% believed PGx is a useful tool and relevant to future practice but over 70% stated they lack confidence in clinical PGx knowledge. This 38-item PGx survey included three factors showing high reliability. Prior genetic/PGx testing and unsatisfactory medication experiences were associated with a more positive attitude toward PGx. Conclusion: The majority of students have positive attitudes toward PGx, but lack knowledge in genetic concepts and clinical PGx.

A pharmacogenomics (PGx) survey with high reliability showed that incoming doctoral pharmacy students have positive attitudes toward PGx, but lack knowledge of genetic concepts and clinical PGx.

The Identification of Novel CYP2D6 Variants in US Hmong: Results From Genome Sequencing and Clinical Genotyping.

Objective: Hmong individuals represent a unique East Asian subpopulation in whom limited information concerning pharmacogenetic variation exists. The objectives of this study were to comprehensively characterize the highly polymorphic CYP2D6 gene in Hmong, estimate allele and phenotype frequencies and to compare results between two testing platforms. Methods: DNA from 48 self-identified Hmong participants were sequenced using a targeted next-generation sequencing (NGS) panel. Star allele calls were made using Astrolabe, manual inspection of NGS variant calls and confirmatory Sanger sequencing. Structural variation was determined by long-range (XL)-PCR and digital droplet PCR (ddPCR). The consensus diplotypes were subsequently translated into phenotype utilizing the activity score system. Clinical grade pharmacogenetic testing was obtained for 12 of the 48 samples enabling an assessment of concordance between the consensus calls and those determined by clinical testing platforms. Results: A total of 13 CYP2D6 alleles were identified. The most common alleles were CYP2D6*10 and its structural arrangements (37.5%, 36/96) and the *5 gene deletion (13.5%, 13/96). Three novel suballeles (*10.007, *36.004, and *75.002) were also identified. Phenotype frequencies were as follows: ultrarapid metabolizers (4.2%, 2/48), normal metabolizers (41.7%, 20/48) and intermediate metabolizers (52.1%, 25/48); none of the 48 participants were predicted to be poor metabolizers. Concordance of diplotype and phenotype calls between the consensus and clinical testing were 66.7 and 50%, respectively. Conclusion: Our study to explore CYP2D6 genotypes in the Hmong population suggests that this subpopulation is unique regarding CYP2D6 allelic variants; also, a higher portion of Hmong participants (50%) are predicted to have an intermediate metabolizer phenotype for CYP2D6 compared to other East Asians which range between 27 and 44%. Results from different testing methods varied considerably. These preliminary findings underscore the importance of thoroughly interrogating unique subpopulations to accurately predict a patient's CYP2D6 metabolizer status.

Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States.

Underrepresentation of subpopulations within geo-ancestral groups engaged in research can exacerbate health disparities and impair progress toward personalized medicine. This is particularly important when implementing pharmacogenomics which uses genomic-based sources of variability to guide medication selection and dosing. This mini-review focuses on pharmacogenomic findings with Hmong in the United States and their potential clinical implications. By actively engaging Hmong community in pharmacogenomic-based research, several clinically relevant differences in allele frequencies were observed within key pharmacogenes such as CYP2C9 and CYP2C19 in Hmong compared to those in either East Asians or Europeans. Additionally, using state-of-the-art genome sequencing approaches, Hmong appear to possess novel genetic variants within CYP2D6, a critical pharmacogene affecting pharmacokinetics of a broad range of medications. The allele frequency differences and novel alleles in Hmong have translational impact and real-world clinical consequences. For example, Hmong patients exhibited a lower warfarin stable dose requirement compared to East Asian patients. This was predicted based on Hmong's unique genetic and non-genetic factors and confirmed using real-world data from clinical practice settings. By presenting evidence of the genetic uniqueness and its translational impact within subpopulations, such as the Hmong, we hope to inspire greater inclusion of other geo-ancestrally underrepresented subpopulations in pharmacogenomic-based research.

Differences in Predicted Warfarin Dosing Requirements Between Hmong and East Asians Using Genotype-Based Dosing Algorithms.

INTRODUCTION: Warfarin's narrow therapeutic index and high variability in dosage requirements make dosage selection critical. Genetic factors are known to impact warfarin dosage selection. The Hmong are a unique Asian subpopulation numbering over 278,000 in the United States whose participation in genetics-based research is virtually nonexistent. The translational significance of early reports of warfarin pharmacogene differences in Hmong has not been evaluated. OBJECTIVES: (i) To validate previously identified allele frequency differences relevant to warfarin dosing in Hmong versus East Asians and (ii) to compare predicted warfarin sensitivity and maintenance doses between a Hmong population and an East Asian cohort. METHOD: DNA collected from two independent cohorts (n=236 and n=198) of Hmong adults were genotyped for CYP2C9 (*2, *3), VKORC1 (G-1639A), and CYP4F2 (*3). Allele frequencies between the combined Hmong cohort (n=433) and East Asians (n=1165) from the 2009 International Warfarin Pharmacogenetics Consortium (IWPC) study were compared using a χ2 test. Percentages of Hmong and East Asian participants predicted to be very sensitive to warfarin were compared using a χ2 test, and the predicted mean warfarin maintenance dose was compared with a t test. RESULTS: The allele frequencies of CYP2C9*3 in the combined Hmong cohort and CYP4F2*3 in the VIP-Hmong cohort are significantly different from those in East Asians (18.9% vs 3.0%, p<0.001 and 9.8% vs 22.1%, p<0.001, respectively). Comparing the combined Hmong cohort to the East Asian cohort, the percentage of participants predicted to be very sensitive to warfarin was significantly higher (28% vs 5%, p<0.01) and the mean predicted warfarin maintenance dose was significantly lower (19.8 vs 21.3 mg/week, p<0.001), respectively. CONCLUSION: The unique allele frequencies related to warfarin when combined with nongenetic factors observed in the Hmong translate into clinically relevant differences in predicted maintenance dose requirements for Hmong versus East Asians.

Potential Clinical Relevance of Differences in Allele Frequencies Found within Very Important Pharmacogenes between Hmong and East Asian Populations.

OBJECTIVES: Implementing pharmacogenetics for very important pharmacogenes (VIPs) holds the promise of improving clinical outcomes through optimal medication selection and dosing. However, significant differences in the frequency of actionable variants in VIPs may exist within subpopulations of a given ancestral group. Furthermore, these differences can potentially impact drug selection and dosing. The purpose of this study was to ascertain allele frequencies for VIPs and to predict medication requirements using Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines in Hmong and compare with published data for East Asians. METHODS: Using a community-based participatory action research approach, DNA collected from 194 Hmong adults living in the United States was analyzed for 22 genetic variants within eight VIPs (CYP2C9, CYP2C19, CYP4F2, DPYD, G6PD, SLCO1B1, TPMT, VKORC1). Allele frequencies for VIPs and predicted medication requirements using CPIC guidelines were compared between Hmong participants and East Asians. RESULTS: Significant differences in allele frequencies between the Hmong and East Asians were found for 23% (5/22) of the CPIC-actionable variants tested. Allele frequencies for VIPs in Hmong versus East Asians were 16.6% versus 3.4% in CYP2C9*3A, 42.2% versus 29.0% for CYP2C19*2, 0.3% versus 8.3% in CYP2C19*3, 6.5% versus 22.1% in CYP4F2*3, and 3.6% versus 0.1% in SLCO1B1*5, respectively. These differences significantly influenced predicted medication usage recommendations in warfarin, simvastatin, and phenytoin between Hmong and East Asians. CONCLUSIONS: Important differences in allele frequencies for key genetic variants influencing selection of medications and dosages were found between the Hmong and East Asians. The magnitude and nature of these differences can be expected to result in different medication recommendations for the Hmong relative to East Asians.

HLA-B*58: 01 carrier status of Hmong in Minnesota: first in Hmong genotyping for prevalence of this biomarker of risk for severe cutaneous adverse reactions caused by allopurinol.

Allopurinol, a common medication to treat gout, is associated with severe cutaneous adverse reactions, and the occurrence is highly predicted by an individual's HLA-B*58:01 carrier status. Guidelines endorse preemptive testing in select Asian populations before initiating allopurinol. The Hmong, an Asian subpopulation originally from China who now live dispersed around the world, have a 2.5-fold higher risk of gout when compared to non-Hmong in Minnesota. Given the concern for severe cutaneous adverse reactions when prescribing allopurinol, we quantified the carrier status of HLA-B*58:01 in Hmong from two independent cohorts in Minnesota. Using a community-based participatory research approach, HLA-B*58:01 carrier status was determined in 49 US-born Hmong without a history of gout or allopurinol use. Further, 47 Hmong patients undergoing clinical evaluation to receive gout pharmacotherapy were also tested. The frequency of HLA-B*58:01 positive carrier status in these two cohorts were compared to published data from a Han Chinese (n = 2910) and a Korean cohort (n = 485) using a Fisher's exact test with a Bonferroni-corrected P-value <0.025 for significance. With one uninterpretable result, we identified two out of 95 people (2.1%) who carried HLA-B*58:01. This 2.1% incidence in these Hmong adults is notably lower than Han Chinese (19.6%, P < 0.0001) and Korean (12.2%, P = 0.0016) populations. Though commonly understood to be of Chinese descent, the lower prevalence within the Hmong underscores the risk of generalizing genotypic findings from Chinese to Asian subpopulations. We suggest no change to the current guidelines recommending which populations should be tested for HLA-B*58:01 before allopurinol use until further validation.

Development of chloroplast microsatellite markers for Glyptostrobus pensilis (Cupressaceae).

PREMISE: Glyptostrobus pensilis (Cupressaceae) is a critically endangered conifer native to China, Laos, and Vietnam, with only a few populations remaining in the wild. METHODS AND RESULTS: Using a complete chloroplast genome sequence, we designed 70 cpSSR loci and tested them for amplification success and polymorphism in 16 samples. Ten loci were found to be polymorphic and their genetic diversity was characterized using a total of 83 individuals from three populations in China. A total of 43 haplotypes were present, the effective number of haplotypes varied from 4.55 to 13.36, and the haplotypic richness ranged from 8.04 to 16.00. Gene diversity ranged from 0.81 to 0.97 (average 0.89). The number of alleles per locus and population ranged from one to eight, and the effective number of alleles ranged from 1.00 to 3.90. All polymorphic loci were successfully amplified in the related species Cryptomeria japonica var. sinensis, Taxodium distichum, T. ascendens, and Cunninghamia lanceolata. CONCLUSIONS: These newly developed chloroplast microsatellites will be useful for population genetic and phylogeographic analyses of G. pensilis and related species.

Medication management in Minnesota schools: The need for school nurse-pharmacist partnerships.

BACKGROUND: Pharmacist participation in school medication management (MM) is minimal. School nurses are responsible for increasingly complex medication administration and management in schools. OBJECTIVES: The purpose of this study was to 1) assess the MM needs of school nurses in Minnesota, and 2) determine if and how interprofessional partnerships between nurses and pharmacists might optimize MM for students. METHODS: Researchers from the University of Minnesota College of Pharmacy, School Nurse Organization of Minnesota, and Minnesota Department of Health conducted a 32-item online survey of school nurses. RESULTS: Nurses administered the majority of medications at their school (69.9%) compared with unlicensed assistive personnel (29%). Stimulants (37.7%), asthma medications (25.7%), over-the-counter analgesics (17.8%), and insulin (6.6%) were the most commonly administered drug therapies. A clear majority of school nurses were interested in partnering with pharmacists: 90.3% thought that a pharmacist could assist with MM, 80% would consult with a pharmacist, and 12.3% reported that they already have informal access to a pharmacist. Topics that nurses would discuss with a pharmacist included new medications (71.6%), drug-drug interactions (67.1%), proper administration (52%), and storage (39.4%). The top MM concerns included 1) availability of students' medications and required documentation, 2) health literacy, 3) pharmacist consultations, 4) lack of time available for nurses to follow up with and evaluate students, 5) family-centered care, 6) delegation, 7) communication, and 8) professional development. CONCLUSION: Although the majority of school nurses surveyed indicated that partnerships with pharmacists would improve school MM, few had a formal relationship. Interprofessional partnerships focused on MM and education are high on the list of services that school nurses would request of a consultant pharmacist. Study results suggest that there are opportunities for pharmacists to collaborate with school nurses; further study is necessary to advance high-quality MM for students in Minnesota schools.

Awareness of state legislation on naloxone accessibility associated with willingness to prescribe naloxone.

BACKGROUND: Increasing rates of opioid-related deaths, state naloxone legislation changes, and negativity prompted investigation of predictive factors associated with willingness to prescribe naloxone to populations at risk of overdose, including knowledge of risk factors, assessment of persons at risk, awareness of legislative changes, perceptions of professional responsibility, and confidence around naloxone prescribing and distribution. METHODS: Cross-sectional, Web-based, anonymous, voluntary survey to prescribers of 2 regional health care systems serving urban and rural North Dakota, northern Minnesota, and northwestern Wisconsin. Human subject research was approved by university and health care systems' institutional review boards. RESULTS: Overall, 203 of 1586 prescribers responded; however, not all prescribers completed each survey item. A majority (89.4%, n = 127/142) of respondents had never prescribed naloxone for overdose prevention. Willingness to prescribe naloxone for 4 patient care scenarios involving substantial opioid overdose risk ranged from 43.4% to 70.5%. Knowledge mean score was 15.5 (SD = 2.9) out of 22 with median 15 (range: 5-22). Naloxone legislation awareness score was 8.8 (SD = 3.8) out of 15 with median 8 (range: 3-15). There was a statistically significant but modest correlation between willingness to prescribe naloxone and the other variables, including awareness of state naloxone-related legislation (r = 0.43, P < .0001), level of self-confidence about dosing, prescribing, and writing protocols for naloxone (r = 0.37, P < .0001), general knowledge (r = 0.24, P = .0032), and perception of professional responsibility (r = 0.19, P = .03). Multivariate regression analysis indicated willingness to prescribe naloxone was associated with statistically significant predictors, including awareness of the naloxone laws (P = .0016) and self-confidence about dosing, prescribing, and writing protocols (P = .0011). CONCLUSIONS: Prescribers who are more aware of state laws regarding naloxone and confident in their knowledge of dosing, administration, and writing protocols may be more willing to prescribe naloxone.

Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population.

OBJECTIVE: Ankylosing spondylitis (AS) is a form of chronic inflammatory spondyloarthritis (SpA) that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27) and B60 (HLA-B60) have been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC) region, showed high sensitivity (98.7%) and specificity (98.0%) for HLA-B27. DESIGN: The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464) can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction. RESULTS: Our results indicated that the relative risk (RR) for HLA-B27+/HLA-B60- was 152 (95% CI 91 to 255) and it increased to 201 (95% CI 85 to 475) in HLA-B27+/HLA-B60+ patients (with HLA-B27-/HLA-B60- as reference). Combinational analysis of two risk factors (HLA-B27+/HLA-B60+) showed a relative excess risk due to interaction (RERI) of 46.79 (95% CI: -117.58 to 211.16), attributable proportion (AP) of 0.23 (95% CI: -0.41 to 0.88) and a synergy index (S) of 1.31 (95% CI: 0.56 to 3.04). CONCLUSION: In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population.

rs10865331 associated with susceptibility and disease severity of ankylosing spondylitis in a Taiwanese population.

Ankylosing spondylitis (AS) is a highly familial rheumatic disorder and is considered as a chronic inflammatory disease. Genetic factors are involved in the pathogenesis of AS. To identify genes which render people susceptible to AS in a Taiwanese population, we selected six single-nucleotide polymorphisms (SNPs) from previous genome-wide association studies (GWASs) which were associated with AS in European descendants and Han Chinese. To assess whether the six SNPs contributed to AS susceptibility and severity in Taiwanese population, 475 AS patients fulfilling the modified New York Criteria and 527 healthy subjects were recruited. We found that rs10865331 was significantly associated with AS susceptibility and with Bath AS Function Index (BASFI). The AA and AG genotypes of rs10865331 were also significantly associated with a higher erythrocyte sedimentation rate. Our findings provided evidence that rs10865331 is associated AS susceptibility and with disease activity (BASFI) in a Taiwanese population.

Close correlation between season of birth and the prevalence of bronchial asthma in a Taiwanese population.

BACKGROUND: Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are common allergic diseases. Environmental factors were indicated to influence the development of allergic diseases. OBJECTIVE: To evaluate the correlation between the month of birth and the prevalence of allergic diseases in Taiwan. METHODS: Data from 104,455 children were collected from the National Insurance Research Database of Taiwan. Subjects were identified by at least two service claims for ambulatory care or one claim for inpatient care. All of the enrolled patients were aged 7∼15 years in 2010. In a bio-clinical data analysis, total immunoglobulin E (IgE) and ImmunoCAP™ allergen data (CAP) from mothers and infants were collected in a medical center in Taiwan. Correlations between children's allergic factors and the season of birth were assessed. RESULTS: A significant difference in the prevalence of BA according to the month of birth (Χ(2) = 18.2, p<0.001) was found in the Taiwanese population. The fewest schoolchildren with were born in May (7.21%), and the most were born in October (10.59%). However, no tendency for the prevalence of AD (Χ(2) = 4.6, P = 0.204) or AR (Χ(2) = 4.3 P = 0.229) was found. In addition, we found that children born in autumn (August to October) had a higher prevalence of BA compared to those born in spring (February to April) (odds ratio: 1.13; 95% confidence interval: 1.05∼1.21). In a bio-clinical data study, markers of maternal and childhood allergies including IgE and CAP were detected in a risk analysis section. Children who were born in autumn had higher levels of CAP and total IgE. CONCLUSIONS: The findings of this study showed that the month of birth was closely correlated with the prevalence of BA and higher levels of CAP and IgE.